This proposal is concerned with examining the effects of changes in the ambient temperature (Ta) on neuropharmacological manipulations of body temperature (Tb) and sleep. Sleep, especially rapid-eye-movement sleep (REMS) is easily disrupted by thermal stress. A drug treatment that alters thermoregulation may alter an animal's zone of thermal comfort, thereby making the Ta at which sleep is being measured more or less stressful, and because of that, decrease or increase REMS. We will examine the effects of Ta on sleep after administration of drugs that affect noradrenergic and serotonergic pathways in the brain, and also after administration of drugs that affect noradrenergic and serotonergic pathways in the brain, and also after administration of two peptides that have been implicated in sleep and thermoregulation. The experiments involve measuring sleep and Tb in unhandled, unrestrained rats, at Ta's at and below a normal rat's thermoneutral zone, after injection of the drugs. We will examine not only the correlation between changes in Tb and changes in sleep, but also measure behavioral thermoregulation to see whether a compound that alters Tb is doing so by changing the animal's regulated level of Tb (thermal setpoint). The drugs to be used are three noradrenergic receptor blocking agents, phentolamine, prazosine and yohimbine; a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA); a serotonin precursor, 5- hydroxytryptophan, a compound that reverses the effects of PCPA; and two putative sleep-promoting substances, cholecystokinin octapeptide and vasoactive intestinal peptide. In view of the amount of effort that goes into trying to understand and treat sleep disorders, especially insomnia, this research should prove useful and timely, and takes a unique approach to these problems.